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282 results on '"Tang, Choong Leong"'

10. Abstract 4119: Anti-KRAS antibody aggregates KRAS in the cytoplasm of live ex vivo cultured human colorectal adenocarcinoma cells and prevents its trafficking to the plasma membrane

Author

Cheah, Peh Yean, primary, Lam, Kuen Kuen, additional, Low, Yee Syuen, additional, Lo, Michelle, additional, Wong, Michelle, additional, Tang, Choong Leong, additional, Tan, Emile, additional, Chok, Aik Yong, additional, En, Issac Seow, additional, and Wong, Siew Heng, additional

Published
2023
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11. The chromatin structuring protein HMGA2 influences human subtelomere stability and cancer chemosensitivity.

Author

Syed Moiz Ahmed, Priya Dharshana Ramani, Stephen Qi Rong Wong, Xiaodan Zhao, Roland Ivanyi-Nagy, Tang Choong Leong, Clarinda Chua, Zhizhong Li, Hannes Hentze, Iain BeeHuat Tan, Jie Yan, Ramanuj DasGupta, and Peter Dröge

Subjects
Medicine, Science
Abstract

The transient build-up of DNA supercoiling during the translocation of replication forks threatens genome stability and is controlled by DNA topoisomerases (TOPs). This crucial process has been exploited with TOP poisons for cancer chemotherapy. However, pinpointing cellular determinants of the best clinical response to TOP poisons still remains enigmatic. Here, we present an integrated approach and demonstrate that endogenous and exogenous expression of the oncofetal high-mobility group AT-hook 2 (HMGA2) protein exhibited broad protection against the formation of hydroxyurea-induced DNA breaks in various cancer cells, thus corroborating our previously proposed model in which HMGA2 functions as a replication fork chaperone that forms a protective DNA scaffold at or close to stalled replication forks. We now further demonstrate that high levels of HMGA2 also protected cancer cells against DNA breaks triggered by the clinically important TOP1 poison irinotecan. This protection is most likely due to the recently identified DNA supercoil constraining function of HMGA2 in combination with exclusion of TOP1 from binding to supercoiled substrate DNA. In contrast, low to moderate HMGA2 protein levels surprisingly potentiated the formation of irinotecan-induced genotoxic covalent TOP1-DNA cleavage complexes. Our data from cell-based and several in vitro assays indicate that, mechanistically, this potentiating role involves enhanced drug-target interactions mediated by HMGA2 in ternary complexes with supercoiled DNA. Subtelomeric regions were found to be extraordinarily vulnerable to these genotoxic challenges induced by TOP1 poisoning, pointing at strong DNA topological barriers located at human telomeres. These findings were corroborated by an increased irinotecan sensitivity of patient-derived xenografts of colorectal cancers exhibiting low to moderate HMGA2 levels. Collectively, we uncovered a therapeutically important control mechanism of transient changes in chromosomal DNA topology that ultimately leads to enhanced human subtelomere stability.

Published
2019
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12. Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas

Author

Thean, Lai Fun, Wong, Michelle, Lo, Michelle, Tan, Iain, Wong, Evelyn, Gao, Fei, Tan, Emile, Tang, Choong Leong, and Cheah, Peh Yean

Abstract

BackgroundColorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aimed to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients.MethodsA case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analysed with the correlation/trend test based on the additive model. SNP variants with association testing −log10 p value ≥5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation.ResultsGlycolysis was uncovered as the top hallmark gene set. Transcripts from two of the five genes profiled, hematopoietic substrate 1 associated protein X 1 (HAX1) and hyaluronan-mediatedmotility receptor (HMMR), were significantly upregulated in the metastasis-positive tumours. In contrast to disease-risk variants, HAX1appeared to act synergistically with HMMRin significantly impacting metastasis-free survival. Examining the subtype datasets with FUMA and Ingenuity Pathway Analysis (IPA) identified distinct pathways demonstrating sexual dimorphism in CRC metastasis.ConclusionsCombining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of patients with stage I-III CRC.

Published
2024
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18. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

Author

Simoni, Yannick, Fehlings, Michael, Kløverpris, Henrik N., McGovern, Naomi, Koo, Si-Lin, Loh, Chiew Yee, Lim, Shawn, Kurioka, Ayako, Fergusson, Joannah R., Tang, Choong-Leong, Kam, Ming Hian, Dennis, Koh, Lim, Tony Kiat Hon, Fui, Alexander Chung Yaw, Hoong, Chan Weng, Chan, Jerry Kok Yen, Curotto de Lafaille, Maria, Narayanan, Sriram, Baig, Sonia, Shabeer, Muhammad, Toh, Sue-Anne Ee Shiow, Tan, Henry Kun Kiaang, Anicete, Rosslyn, Tan, Eng-Huat, Takano, Angela, Klenerman, Paul, Leslie, Alasdair, Tan, Daniel S.W., Tan, Iain Beehuat, Ginhoux, Florent, and Newell, Evan W.

Published
2017
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21. Gracilis pull-through flap for the repair of a recalcitrant recto-vaginal fistula

Author

James Mok, Wan Loong, Goh, Ming Hui, Tang, Choong Leong, and Tan, Bien Keem

Subjects
medicine.medical_specialty, medicine.medical_treatment, Fistula, lcsh:Surgery, Case Report, 030230 surgery, Rectovaginal fistula, 03 medical and health sciences, 0302 clinical medicine, Colorectal surgery, Reconstructive surgical procedures, medicine, Gracilis muscle, business.industry, Colostomy, lcsh:RD1-811, Anus, medicine.disease, Surgery, Tendon, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Vagina, business
Abstract

Recto-vaginal fistulas are difficult to treat due to their high recurrence rate. Currently, no single surgical intervention is universally regarded as the best treatment option for rectovaginal fistulas. We present a case of recurrent recto-vaginal fistula surgically treated with a gracilis pull-through flap. The surgical goals in this patient were complete excision of the recto-vaginal fistula and introduction of fresh, vascularized muscle to seal the fistula. A defunctioning colostomy was performed 1 month prior to the present procedure. The gracilis muscle and tendon were mobilized, pulled through the freshened recto-vaginal fistula, passed through the anus, and anchored externally. Excess muscle and tendon were trimmed 1 week after the procedure. Follow-up at 4 weeks demonstrated complete mucosal coverage over an intact gracilis muscle, and no leakage. At 8 weeks post-procedure, the patient resumed sexual intercourse with no dyspareunia. At 6 months post-procedure, her stoma was closed. The patient reported transient fecal staining of her vagina after stoma reversal, which resolved with conservative treatment. The fistula had not recurred at 20 months post-procedure. The gracilis pull-through flap is a reliable technique for a scarred vagina with an attenuated rectovaginal septum. It can function as a well-vascularized tissue plug to promote healing.

Published
2019

42. The orphan nuclear receptorNR0B2could be a novel susceptibility locus associated with microsatellite‐stable,APCmutation‐negative early‐onset colorectal carcinomas with metabolic manifestation

Author

Lam, Kuen Kuen, primary, Sethi, Raman, additional, Tan, Grace, additional, Tomar, Swati, additional, Lo, Michelle, additional, Loi, Carol, additional, Tang, Choong Leong, additional, Tan, Emile, additional, Lai, Poh San, additional, and Cheah, Peh Yean, additional

Published
2020
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47. The evaluation of CEEA 34 for stapled hemorrhoidectomy: results of a prospective clinical trial and patient satisfaction

Author

Chew, Min-Hoe, Kam, Ming-Hian, Lim, Jit-Fong, Ho, Kok-Sun, Ooi, Boon-Swee, Tang, Choong-Leong, and Eu, Kong-Weng

Subjects
Hemorrhoids, Clinical trials, Patient satisfaction, Health
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2008.01.033 Byline: Min-Hoe Chew, Ming-Hian Kam, Jit-Fong Lim, Kok-Sun Ho, Boon-Swee Ooi, Choong-Leong Tang, Kong-Weng Eu Keywords: Stapled hemorrhoidectomy; Technique; Modification; Quality of life Abstract: Stapled hemorrhoidectomy (SH) has routinely been performed using Procedure for Prolapse and Hemorrhoids Proximate Hemorrhoidal Circular Staplers (Ethicon Endo-surgery, Cincinnati, OH). Premium Plus CEEA 34 (Tyco Healthcare, New Haven, CT) has been recently introduced for SH. This study aims to review the effectiveness of CEEA 34 for SH. Author Affiliation: Department of Colorectal Surgery, Singapore General Hospital, Outram Road, Singapore 169608 Article History: Received 18 November 2007; Revised 2 January 2008

Published
2009

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